Anti-inflammatory Effects of Nortrachelogenin in Murine J774 Macrophages and in Carrageenan-Induced Paw Edema Model in the Mouse

Mirka Laavola; Tiina Leppänen; Heikki Eräsalo; Mari Hämäläinen; Riina Nieminen; Eeva Moilanen

doi:10.1055/s-0042-118188

Planta Medica, Table of Contents

Planta Med 2017; 83(06): 519-526
DOI: 10.1055/s-0042-118188

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Anti-inflammatory Effects of Nortrachelogenin in Murine J774 Macrophages and in Carrageenan-Induced Paw Edema Model in the Mouse

Mirka Laavola

The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland

,

Tiina Leppänen

The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland

,

Heikki Eräsalo

The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland

,

Mari Hämäläinen

The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland

,

Riina Nieminen

The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland

,

Eeva Moilanen

The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland

› Author Affiliations

Abstract

Nortrachelogenin is a pharmacologically active lignan found in knot extracts of Pinus sylvestris. In previous studies, some lignans have been shown to have anti-inflammatory properties, which made nortrachelogenin an interesting candidate for our study. In inflammation, bacterial products and cytokines induce the expression of inducible nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E synthase-1. These enzymes synthesize factors, which, together with proinflammatory cytokines, are important mediators and drug targets in inflammatory diseases.

The effects of nortrachelogenin on the expression of inducible nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E synthase-1 as well as on the production of nitric oxide, prostaglandin E₂, and cytokines interleukin-6 and monocyte chemotactic protein-1 were investigated in the murine J774 macrophage cell line. In addition, we examined the effect of nortrachelogenin on carrageenan-induced paw inflammation in mice.

Interestingly, nortrachelogenin reduced carrageenan-induced paw inflammation in mice and inhibited the production of inflammatory factors nitric oxide, prostaglandin E₂, interleukin-6, and monocyte chemotactic protein-1 in J774 macrophages in vitro. Nortrachelogenin inhibited microsomal prostaglandin E synthase-1 protein expression but had no effect on cyclooxygenase-2 protein levels. Nortrachelogenin also had a clear inhibitory effect on inducible nitric oxide synthase protein expression but none on its mRNA levels, and the proteasome inhibitor lactacystin reversed the effect of nortrachelogenin on inducible nitric oxide synthase expression, suggesting a post-transcriptional mechanism of action.

The results revealed hitherto unknown anti-inflammatory properties of nortrachelogenin, which could be utilized in the development of anti-inflammatory treatments.

Key words

nortrachelogenin - lignan - iNOS - inflammation - Pinus sylvestris - Pinaceae

Full Text

References

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